General Characteristics of Viruses

Structure
Because most viruses are extremely well adapted to their host organism, virus structure
varies greatly. However, there are some general structural characteristics that all viruses
share.

Figure 1.1: General virus structure

All viruses have a capsid or head region that contains its genetic material.
The capsid is made of proteins and glycoproteins.
Capsid construction varies greatly among viruses, with most being specialized for a
particular virus's host organism.
Some viruses, mostly of the type infecting animals, have a membranous envelope
surrounding their capsid. This allows viruses to penetrate host cells through membrane
fusion.
The virus's genetical material rests inside the capsid; that material can be either DNA,
RNA.
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In addition to the head region, some viruses, mostly those that infect bacteria, have a tail
region. The tail is an often elaborate protein structure. It aids in binding to the surface of
the host cell and in the introduction of virus genetic material to the host cell.

Though the details of virus infection and replication vary greatly with host type, all
viruses share 6 basic steps in their replication cycles. These are:
1) attachment - The virus must first attach itself to the host cell

2) penetration - Either of the whole virus or just the contents of the capsid.

3) uncoating - If the entire capsid enters, the genetic material must be uncoated to make
it available to the cell's replication machinery

4) replication - Replication of genetic material takes place, as well as the production of

capsid and tail proteins

5) assembly - Once all of the necessary parts have been replicated, individual virus
particles are assembled

6)release- Release often takes place in a destructive manner, bursting and killing the
host cell

Genetic Material

Viruses may carry DNA or RNA as their genetic material. DNA may be single- or double-
stranded (ssDNA and dsDNA), and it may be circular or linear.
The Discovery of Bacteriophage
Bacteriophages are bacterial viruses that attach to their specific hosts and kill them by
internal replication and bacterial lysis. According to most estimates, bacteriophages
inhabited Earth about 3-5 billion years ago, and since that time they have controlled the
levels of bacteria in the environment via a classical predator-prey relationship.
However, the existence of bacteriophages was not known until the early part of the 20th
century, when they were first identified by Frederick Twort and Felix dHerelle who
called them bacteriophages or bacteria-eaters (from the Greek phago meaning to eat or
devour). At that time, with the age of antibiotics still in the future, bacteriophages were
considered to be a powerful cure for bacterial infections, and they were therapeutically
utilized throughout the world during the pre-antibiotic era. Although exact numbers are
impossible to calculate, it is likely that millions of people have been treated with various
therapeutic phage preparations. Bacteriophages naturally inhabit various parts of the
human body (e.g., the mouth, skin, gastrointestinal tract, etc.) and humans daily eat many
foods containing bacteriophages.

Numerous published studies have indicated that the therapeutic use of phages in humans
and animals is very safe; i.e., serious adverse reactions have never been reported.
However, since some early studies reported that phage therapy was not always effective,
the advent of antibiotics (which seemed to be like magic bullets against numerous
pathogenic bacteria) gradually caused phage therapy to fall out-of-favor in the United
States and Western Europe. Several factors (reviewed in more detail in 1,2), including the
lack of a general understanding of phage biology and imperfections in the diagnostic
bacteriology techniques available at that time, contributed to the failure of some of the
early phage therapy studies and to the associated decline of interest in phage therapy in
the West. However, at the same time, phage therapy continued to be utilized in the former
Soviet Union (FSU) and in various other countries of Eastern Europe. In the FSU and
Eastern Europe and during the pre-antibiotic era, in the United States, Western
Europe and Australia phage therapy was used to treat a wide range of bacterial
infections, ranging from skin infections to septicemia. Among the many routes of phage
administration, oral and topical routes were the most frequently used.

The rapid and alarming emergence of antibiotic-resistant superbugs has rekindled

interest in phage therapy in the West. Intralytix, Inc., is one of the pioneering USA
companies working to develop and commercialize therapeutic phages. Our approach is
based on the results of research supporting the belief that bacteriophages can help to
solve problems regarding (i) bacterial contamination during food processing, (ii) hospital
and environmental sanitation, and (iii) human and animal diseases caused by pathogenic
bacteria, including antibiotic-resistant bacteria.

References:

1. Summers, W. C., Bacteriophage therapy, Annu Rev Microbiol 55, 437-51, 2001.
2. Sulakvelidze, A., Alavidze, Z., and Morris, J. G., Jr., Bacteriophage therapy,
Antimicrob Agents Chemother 45 (3), 649-659, 2001.
Virus "Life" Cycles
Some viruses have a slightly more complicated replication cycle involving lytic and
lysogenic phases.
The lytic phase is similar to that described above, with virus particles infecting and being
replicated.
In the lysogenic phase, however, viral genetic material that has entered the host cell
becomes incorporated in the cell and lies dormant.
It is passed on to the progeny of the infected cells.
Eventually, the lytic phase will start again, and cells that were never infected themselves,
but carry the viral genetic material will begin to produce new virus particles.

Figure1.2: Generalized Replication of Viruses